Background: Despite using Citrullus colocynthis on treatment of various diseases, serious gastrointestinal disorders like bleeding are reported. In Traditional Iranian Medicine (TIM), administering equal weights of starch with this plant is suggested to produce more tolerable preparations from it. Hence, we assessed histopathological changes in rat liver and intestine after using starch as corrective agent.Methods: We designed three experiments in Veterinary Medicine School of Shahid Bahonar University in Kerman, Iran in 2016. The procedure was applied in 2016 for 15 days. In the first experiment, group No. 2 and 3 received single daily dose of alcoholic pulp extract of C. colocynthis at 300 and 600 mg/kg extract consecutively. In the second experiment, group No. 4 and 5 received 300 and 600 mg/kg extract plus the same amount of starch consecutively. In the third experiment, group No. 6 and 7 received extract at 300 and 600 mg/kg plus the three times weight of starch consecutively. The live rats were euthanized and their liver and intestine were removed for histopathology examination. The samples were stained with hematoxyline-eosin (H&E).Results: Rats in all of the groups died from bleeding and diarrhea except for group No.6 that showed no symptoms seen in other rats. Microscopic examination of their intestine showed no histopathological lesions or other degenerative changes of the epithelium.Conclusion: Clearly further works in modern phytotherapy will be required to delineate the role of starch in reducing C. colocynthis toxicity. Consumption of adequate weight of starch with the toxic dose of C. colocynthis make it safe for digestive system but could not prevent necrotic changes in the liver.